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Dnmt3a2: a hub for enhancing cognitive functions

Molecular Psychiatry volume 21, pages 1130–1136 (2016)Cite this article

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Abstract

The mechanisms responsible for fear memory formation and extinction are far from being understood. Uncovering the molecules and mechanisms regulating these processes is vital for identifying molecular targets for the development of novel therapeutic strategies for anxiety and fear disorders. Cognitive abilities require the activation of gene expression necessary to the consolidation of lasting changes in neuronal function. In this study we established a key role for an epigenetic factor, the de novo DNA methyltransferase, Dnmt3a2, in memory formation and extinction. We found that Dnmt3a2 overexpression in the hippocampus of young adult mice induced memory enhancements in a variety of situations; it converted a weak learning experience into long-term memory, enhanced fear memory formation and facilitated fear memory extinction. Dnmt3a2 overexpression was also associated with the increased expression of plasticity-related genes. Furthermore, the knockdown of Dnmt3a2 expression impaired the animals’ ability to extinguish memories, identifying Dnmt3a2 as a key player in extinction. Thus, Dnmt3a2 is at the core of memory processes and represents a novel target for cognition-enhancing therapies to ameliorate anxiety and fear disorders and boost memory consolidation.

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Acknowledgements

We thank Dr AM Hagenston for comments on the manuscript and Stephanie Rothe for her contribution during the initial stages of this project. We thank KĂĽbra GĂĽlmez and Benjamin Zeuch for technical help during the revision stage of the manuscript. This work was supported by the Sonderforschungsbereich (SFB) 636 of the Deutsche Forschungsgemeinschaft (DFG) and an ERC Advanced Grant. HB and AMMO are members of the Excellence Cluster CellNetworks at Heidelberg University. AMMO is a recipient of an Emmy Noether grant from the DFG.

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  1. Department of Neurobiology, Interdisciplinary Center for Neuroscience (IZN), University of Heidelberg, Heidelberg, Germany

    A M M Oliveira, T J Hemstedt, H E Freitag & H Bading

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  1. A M M Oliveira
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  2. T J Hemstedt
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  3. H E Freitag
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  4. H Bading
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Correspondence to H Bading.

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Oliveira, A., Hemstedt, T., Freitag, H. et al. Dnmt3a2: a hub for enhancing cognitive functions. Mol Psychiatry 21, 1130–1136 (2016). https://doi.org/10.1038/mp.2015.175

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